X-ray imaging is a well known and extremely valuable tool for the early detection and diagnosis of various disease states in the human body. The use of contrast agents for image enhancement in medical x-ray imaging procedures is widespread. An excellent background on iodinated and other contrast agents for medical imaging is provided by D.P. Swanson et al, Pharmaceuticals in Medical Imaging, 1990, MacMillan Publishing Company.
U.S. Pat. No. 3,097,228 describes derivatives of 2,4,6-triiodobenzoyloxyalkanoic acids having the structure ##STR2## wherein R.sup.1 is H or lower alkyl; R.sup.2 is H or lower-alkanoyl; and R.sup.3 is H or lower alkanoylamino and R.sup.4 is lower alkyl.
U.S. Pat. No. 3,144,479 describes iodinated benzoic acid esters having the formula ##STR3## wherein X is an iodine atom or an amino group and R is selected from H, alkyl, alkoxyalkyl, i.e., --CH.sub.2).sub.m --O--R", wherein R" is alkyl and m is 1 or 2, phenyl and a particular iodinated aromatic group.
Obendorf (Chem. Abstract 57:4603i) discloses the compound ##STR4## However, this compound has an unacceptably low melting point to be suitably formulated in nanoparticulate x-ray contrast compositions.
Siggins et al (J. Med. Chem. 8(5), 728-30 (1965)) describe iodobenzoates for myelography. However, all of the described compounds are monoiodobenzoates containing less than 40% iodine by weight intended to be intracisternally administered as an oil.
EP-A 498,482 describes nanoparticulate x-ray contrast compositions which have proven to be extremely useful in medical imaging. However, particulate contrast agents in certain in vivo applications can exhibit less than fully satisfactory solubility profiles and/or enzymatic degradation, e.g., in plasma and blood.
It would be desirable to provide compounds for use as x-ray contrast agents having improved enzymatic degradability and appropriate solubility profiles.